Adenocarcinoma of the pancreas is the fifth most common cause of cancer deaths in both men and women in the United States. The 5-year survival rate is about 4%, which is the lowest of any cancer. Recent advances in proteomic research have led to the discovery of disease-related proteins that circulate in the blood. Such proteins may provide a non-invasive means for detecting and monitoring cancer. Novel biomarkers for pancreatic adenocarcinoma are needed since currently available markers have limited clinical utility. The most widely used pancreatic tumor marker, CA 19-9, has high variability and is often undetectable in serum of patients with small tumors. Two proteins, haptoglobin and serum amyloid A, have been detected in the serum of patients with various cancers as well as a mouse model of pancreatic cancer. However, these proteins have not been adequately evaluated in humans with pancreatic adenocarcinoma. The goal of this project is to investigate the potential clinical utility of haptoglobin and serum amyloid A for detecting pancreatic adenocarcinoma. Specifically, we intend to determine if serum levels of these proteins are significantly elevated in patients with pathologically verified disease, determine if serum levels correlate with measures of tumor severity, and assess the relative accuracy for haptoglobin, serum amyloid A and CA 19-9 in distinguishing those patients with pancreatic adenocarcinoma from age and gender matched controls. In this study's second phase, we will use serum levels of haptoglobin and serum amyloid A to evaluate members of families identified through the Utah Population Database to be at high risk for pancreatic cancer. This work has direct health-related significance in identifying improved screening tests for pancreatic cancer.